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1.
Eicosapentaenoic acid (EPA) metabolism into 3 series cyclooxygenase and 5 series lipoxygenase products was assessed in human and rabbit anterior uvea. Both tissues synthesized 3 series cyclooxygenase products such as delta17 6-keto-PGF1 (PGI3 metabolite), PGE3 alpha, PGE3, PGD3 and TxB3 (a stable product of TxA3) and lipoxygenase products 12-hydroxyeicosapentaenoic acid (HEPE), 5-HEPE and 5,12-diHEPE from 14C-EPA. EPA-derived cyclooxygenase product synthesis was considerably greater than the formation of lipoxygenase products from EPA in both tissues. 相似文献
2.
Structure-activity relationships are described for a series of succinyl hydroxamic acids 1a-o and their carboxylic acid analogues 2a-o as inhibitors of matrix metalloproteases MMP-3 and MMP-2. For this series (P1' = (CH2)3Ph, P2' = t-Bu) selectivity for the inhibition of MMP-2 was found to be strongly dependent on P3'. 相似文献
3.
Cepa MM Tavares da Silva EJ Correia-da-Silva G Roleira FM Teixeira NA 《Steroids》2008,73(14):1409-1415
A series of 5alpha-androst-3-enes and 3alpha,4alpha-epoxy-5alpha-androstanes were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. In these series the original C-17 carbonyl group was replaced by hydroxyl, acetyl and hydroxyimine groups. Inhibition kinetic analysis on the most potent steroid of these series revealed that it inhibits the enzyme in a competitive manner (IC(50)=6.5 microM). The achieved data pointed out the importance of the C-17 carbonyl group in the D-ring of the studied steroids as a structural feature required to reach maximum aromatase inhibitory activity. Further, at least one carbonyl group (C-3 or C-17) seems to be essential to effective aromatase inhibition. 相似文献
4.
Three consensus 3D-QSAR (c-3D-QSAR) models were built for 38, 34, and 78 inhibitors of β-secretase, histone deacetylase, and
farnesyltransferase, respectively. To build an individual 3D-QSAR model, the structures of an inhibitor series are aligned
through docking of a protein receptor into the active site using the program GOLD. CoMFA, CoMSIA, and Catalyst are then performed
for the training set of each structurally aligned inhibitor series to obtain a 3D-QSAR model. Since the consensus in features
identified is high for the same pharmacophore features selected for building a 3D-QSAR model by a 3D-QSAR method, a c-3D-QSAR
model for each inhibitor series is constructed by combining the pharmacophore features selected for building the 3D-QSAR model
using the SYBYL spread sheet and PLS module. Each c-3D-QSAR pharmacophore model built was examined visually and compared with
that obtained by simultaneous mapping of the corresponding 3D-QSAR pharmacophores built onto a selected inhibitor structure.
It was found that the c-3D-QSAR model built for an inhibitor series improves not only the overall prediction statistics for
both training and test sets but also the prediction accuracy for some less active inhibitors of the series. 相似文献
5.
Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives 总被引:1,自引:0,他引:1
Tosco P Bertinaria M Di Stilo A Cena C Sorba G Fruttero R Gasco A 《Bioorganic & medicinal chemistry》2005,13(15):4750-4759
Synthesis and pharmacological characterisation of a series of compounds in which the oxime substructure present in imoproxifan was constrained in the pentatomic NO-donor furoxan ring, as well as their structurally related furazan analogues devoid of NO-donating properties, are described. The whole series of products displayed reversible histamine H3-antagonistic activity on guinea-pig ileum. 4-(4-(3-(1H-Imidazol-4-yl)propoxy)phenyl)furoxan-3-carbonitrile 16 was also able to induce partial relaxation when added to the bath after electrical contraction of the guinea-pig ileum during the study of its H3-antagonistic properties. This phenomenon seems to be dependent on NO-mediated sGC activation. The lipophilic-hydrophilic balance of all the products was investigated. 相似文献
6.
Abram L. Wagner Xiaodong Sun JoLynn P. Montgomery Zhuoying Huang Matthew L. Boulton 《PloS one》2014,9(5)
Background
Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugate vaccine (PCV) are relatively expensive, newly introduced vaccines in China. This study evaluates the impact of residency and urbanicity on Hib vaccine and PCV coverage for children aged 2 to 7 years living in Shanghai, China, in August 2012.Methods
In this exploratory cohort study, a sample of children aged 2 to 7 years, all of whom were eligible to have received the complete series of Hib vaccine and PCV, was obtained from the Shanghai Immunization Program Information System. Three measures of vaccination coverage for Hib vaccine and PCV were examined: dose 1 coverage, series completion, and timeliness of dose 1 vaccination. Multivariable binomial regression was used to estimate the difference in vaccination coverage between locals and the floating population.Results
Dose 1 coverage was 50.9% for Hib vaccine and 11.4% for PCV for the 28,141 abstracted pediatric records. For both vaccines, dose 1 coverage was higher in locals than in the floating population. The disparity in coverage between locals and the floating population was greater in suburban areas than urban areas. Of all children who received dose 1, 79.7% completed the Hib vaccine series, and 91.3% completed the PCV series. Timely dose 1 coverage was 8.2% for Hib vaccine and 0.5% for PCV.Conclusion
Low vaccination coverage and extremely low levels of timely dose 1 vaccination indicate that current vaccination efforts are inadequate to reduce the burden of Hib and pneumococcal disease among Chinese children, especially infants. Government funding of the Hib vaccine and PCV through the Expanded Program on Immunization would increase uptake and could also ensure that improvement in the timeliness of administration and series completion is targeted for all demographic groups. 相似文献7.
Under study were the popliteal lymph nodes of rats at different times after total irradiation of animals (the 1st series), total irradiation with screening the left node (the 2nd series) and local screening of other parts of the body (the 3rd series). X-ray irradiation in all experiments was performed under standard conditions in dosage of 800 r. The amount of mitoses (MC 0/00) in light centers and cortical substance was counted in addition to histological alterations. In shielded lymph nodes (2nd series) mediate effects of irradiation were observed characterized by a decrease of the MK amount and massive death of lymphocytes in later terms than after direct effects (1st series). In irradiated nodes (3rd series) the reparative process was more rapid than in the first series due to migration of lymphocytes from non-irradiated parts of the body. The mediate effect of radiation results also in increased amount of plasma cells in lymphatic nodes of animals subjected to total irradiation (1st and 2nd series). It is suggested by the absence of such increase of amount of plasma cells in locally irradiated lymphatic nodes when screening other parts of the body (3rd series). availability of individual distinctions in the character of the lymphoid tissue response to effects of ionizing radiation puts a question of division of experimental animals at least into 2 subgroups which have different indices of proliferative processes. 相似文献
8.
Figueiredo JM Câmara CA Amarante EG Miranda AL Santos FM Rodrigues CR Fraga CA Barreiro EJ 《Bioorganic & medicinal chemistry》2000,8(9):2243-2248
This paper describes recent results of design, synthesis and pharmacological evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds, belonging to the 2-methyl-imidazolyl-3-acylhydrazone class (4a-e). These compounds were planned by applying the molecular simplification strategy to propose the structural modifications on the previously described functionalized imidazo [1,2-a]pyridine 3-acylhydrazone series (2), which presented an important analgesic profile. This new series (4) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series. 相似文献
9.
Martin Lundsgaard Hansen Eva Fallentin Carsten Lauridsen Ian Law Birgitte Federspiel Lene B?ksgaard Lars Bo Svendsen Michael Bachmann Nielsen 《PloS one》2014,9(5)
Objectives
To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer.Materials and Methods
Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ) and stomach were included. Patients received three series of chemotherapy before surgery, each consisting of a 3-week cycle of intravenous epirubicin, cisplatin or oxaliplatin, concomitant with capecitabine peroral. The patients were evaluated with a CT perfusion scan prior to, after the first series of, and after three series of chemotherapy. The CT perfusion scans were performed using a 320-detector row scanner. Tumour volume and perfusion parameters (arterial flow, blood volume and permeability) were computed on a dedicated workstation with a consensus between two radiologists. Response to chemotherapy was evaluated by two measures. Clinical response was defined as a tumour size reduction of more than 50%. Histological response was evaluated based on residual tumour cells in the surgical specimen using the standardized Mandard Score 1 to 5, in which values of 1 and 2 were classified as responders, and 3 to 5 were classified as nonresponders.Results
A decrease in tumour permeability after one series of chemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumour volume were apparent after three series of chemotherapy in both clinical and histological responders. A cut-off value of more than 25% reduction in tumour permeability yielded a sensitivity of 69% and a specificity of 58% for predicting clinical response.Conclusion
Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes. 相似文献10.
Carato P Graulich A Jensen N Roth BL Liégeois JF 《Bioorganic & medicinal chemistry letters》2007,17(6):1570-1574
In continuation of our work on N-(piperidin-4-yl)-naphthamides, the effect of substituted benzyl groups on D(2L), D(4.2), and 5-HT(2A) receptor affinity was evaluated. In the 1-naphthamide series most compounds were highly selective for D(4.2) over D(2L) and 5-HT(2A) receptors. Halogen and methyl substitution in position 3 or 4 of the benzyl group increased D(4.2) affinity. In the 2-naphthamide series a similar high D(4.2) over D(2L) selectivity was retained while 5-HT(2A) affinity was increased. 3-Methoxy, 3-methyl, and 4-methyl substituents were favorable for D(4.2) affinity while halogens reduced affinity. 2-Naphthamides with a 3-bromo- or a 3-methyl group were mixed D(4.2)/5-HT(2A) ligands similar to their unsubstituted parent compound. All compounds from both series with significant affinity for D(4.2) and 5-HT(2A) receptors were antagonists. 相似文献
11.
Hartz RA Arvanitis AG Arnold C Rescinito JP Hung KL Zhang G Wong H Langley DR Gilligan PJ Trainor GL 《Bioorganic & medicinal chemistry letters》2006,16(4):934-937
A novel series of 2-anilino-3-phenylsulfonyl-6-methylpyridines was synthesized and evaluated as corticotropin-releasing factor receptor ligands. Structure-activity relationship studies focused primarily on optimization of the 3-phenylsulfonyl group. Compounds within this series were identified which showed potent binding affinity for the CRF1 receptor. Selected compounds were examined in a rat pharmacokinetic study and were found to have oral bioavailabilities ranging from 16 to 35%. 相似文献
12.
Wang LY Tseng WC Wu TS Kaneko K Takayama H Kimura M Yang WC Wu JB Juang SH Wong FF 《Bioorganic & medicinal chemistry letters》2011,21(18):5358-5362
An efficient 1,3-dipolar cycloaddition method was performed for the synthesis of a series of monofluoro- and trifluoromethane-3,5-disubstituted 1,2,4-triazoles. This efficient cycloaddition method was to react hydrazonoyl hydrochlorides with a series of aldehydes in the presence of NEt(3) as catalytic basic agent to provide the corresponding product in 28-94%. Their growth inhibitory results against cancer cells indicated that some of the fluorine- and trifluoromethane-containing compounds could effectively inhibit the growth of NCI-H226 and T-cell leukemia (Jurkat) cells. Among the compounds, trifluoromethane-containing 1,2,4-triazoles possessed the five-membered ring groups on the C-5 position of the triazolic ring, including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl, possessed the significant inhibitory activity for NCI-H226 cancer cells. 相似文献
13.
Expression of human apolipoprotein A-I epitopes in high density lipoproteins and in serum 总被引:1,自引:0,他引:1
The expression and immunoreactivity of apolipoprotein (apo) A-I epitopes in high density lipoproteins (HDL) and serum has been investigated using two series of monoclonal antibodies (Mabs) which have been described elsewhere. Series 1 Mabs, identified as 3D4, 6B8, and 5G6, were obtained by immunization and screening with apoA-I, and series 2 Mabs, identified as 2F1, 4H1, 3G10, 4F7, and 5F6, were obtained by immunization and screening with HDL. These Mabs were characterized with respect to their binding to HDL particles in solution. In series 2 Mabs, 2F1, 3G10, and 4F7, which react with apoA-I CNBr-fragments 1 and 2, could precipitate 100% of 125I-labeled HDL, while 4H1 and 5F6, which react with CNBr fragments 1 and 3, precipitated 90 and 60% of 125I-labeled HDL, respectively. Therefore, three distinct epitopes mapped to CNBr fragments 1 and 2 have been identified which are expressed on all HDL particles, indicating that several antigenic do mains exist on apoA-I which have the same conformation on all apoA-I-containing lipoproteins. The Mabs reacting at these sites have significantly higher affinity constants for 125I-labeled HDL than those that failed to precipitate 100% of HDL. This suggests that the high affinity Mabs react with apoA-I epitopes that are both expressed on all lipoproteins and located in thermo-dynamically stable regions of the molecules. All Mabs from series 1 precipitated 35% or less of 125I-labeled HDL prepared from freshly collected serum, but the proportion of HDL particles expressing the epitopes for these Mabs doubled or more upon serum storage at 4 degrees C. The time course of the alteration of apoA-I antigen in vitro was measured in three normolipemic donors. Upon storage of serum at 4 degrees C, the immunoreactivity of series 2 Mabs (4H1, 3G10) remained unchanged. However, the immunoreactivity of series 1 Mab 3D4 increased linearly at 38%/day for 4 weeks and by 12 weeks had plateaued at about 280-fold compared to day 1. The immunoreactivity of other series 1 Mabs also increased significantly with time in vitro. This process was partially inhibited in the presence of EDTA and by addition of antioxidants, however, the exact molecular nature of this in vitro alteration of apoA-I antigen was not identified. 相似文献
14.
Tran JA Tucci FC Arellano M Jiang W Chen CW Marinkovic D Fleck BA Wen J Foster AC Chen C 《Bioorganic & medicinal chemistry letters》2008,18(6):1931-1938
Based on 3-phenylpropionamides, a series of 3-arylpyrrolidine-2-carboxamide derivatives was designed and synthesized to study the effect of cyclizations as melanocortin-4 receptor ligands. It was found that the 2R,3R-pyrrolidine isomer possessed the most potent affinity among the four stereoisomers. 相似文献
15.
Kang TS Jo HO Park WK Kim JP Konishi Y Kong JY Park NS Jung YS 《Bioorganic & medicinal chemistry letters》2008,18(5):1663-1667
A series of 3,5-dialkoxy-4-hydroxycinnamamides 6 and 7 was synthesized, and their antioxidant activity was assessed using the thiobarbituric acid reactive substance (TBARS) assay. Interestingly, cinnamamides with longer alkoxy groups on the C-3 and C-5 positions display enhanced inhibition, and most of the compounds in the series tested exhibit excellent lipid peroxidation inhibitory activities. Some cinamamides bearing hexyloxy or 2,6-di-tert-butyl-4-methyl phenol groups have submicromolar inhibitory activities. 相似文献
16.
The aim of this study was to estimate the BOD(5) and COD removal efficiency and biomass yield coefficient in sequencing batch reactors (SBR) treating landfill leachate. Experiments were carried out in four SBRs at HRT of 12, 6, 3 and 2d. Two series were performed. In series 1, the reactors were operated in a 24h cycle mode (anoxic 3h, aeration 18 h, settling 2.75 h, and discharge 0.25 h). In series 2, however, the anoxic phase was eliminated. In both series the BOD(5) removal efficiency was almost identical--over 98%. On shortening HRT from 12 to 2d, COD removal efficiency decreased from 83.1% to 76.7% (series 1). In series 2, efficiency ranged from 79.6% to 75.7%. In the reactors working with the anoxic phase the observed biomass yield coefficient (Y(obs)) was nearly constant (0.55-0.6 mg VSS/mg COD). Upon elimination of the anoxic phase, the Y(obs) was observed to decrease from 0.32 mg VSS/mg COD (HRT 2d) to 0.04 mg VSS/mg COD (HRT 12d). 相似文献
17.
Kim HS Khan SN Jadhav JR Jeong JW Jung K Kwak JH 《Bioorganic & medicinal chemistry letters》2011,21(13):3861-3865
A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial activities against Gram-positive strains. Compound 18 was found to be the most potent in these series with a MIC value as low as 1 μg/mL against the bacterium Staphylococcus aureus ATCC6538P. 相似文献
18.
Jin-Cherng Lien Li-Jiau Huang Jih-Pyang Wang Che-Ming Teng Kuo-Hsiung Lee Sheng-Chu Kuo 《Bioorganic & medicinal chemistry》1997,5(12):2111-2120
A series of 2-substituted 3-chloro-1,4-naphthoquinones was synthesized, and the antiplatelet, antiinflammatory, and antiallergic activities of these compounds were evaluated. The structure-activity relationships in this series were also examined. Most of the 2-alkyl/arylcarboxamido derivatives of 3-chloro-1,4-naphthoquinone showed potent activities with similar trends in each of the activities evaluated. 相似文献
19.
Kadri H Matthews CS Bradshaw TD Stevens MF Westwell AD 《Journal of enzyme inhibition and medicinal chemistry》2008,23(5):641-647
A new series of fluorinated and non-fluorinated 2-phenylbenzimidazoles bearing oxygenated substituents on the phenyl ring has been synthesized. Synthesis of the new series was based on our previous discovery of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610) as a potent and selective antitumour agent in vitro (sub-nanomolar GI(50) in sensitive human cancer cell lines), but with poor aqueous solubility and lack of a definitive cellular target limiting further development. In this study we test the hypothesis that 2-phenylbenzimidazoles with similar substitution patterns to PMX 610 would retain potent antitumour activity but with potentially superior pharmaceutical properties. In general the new compounds were less active than the former benzothiazole series in vitro when tested against the breast cancer cell lines MCF-7 and MDA 468; however the two most active compounds in the present series (3j and 3k) exhibit low micromolar GI(50) values in both cell lines and provide the opportunity for further chemical derivatization with a view to target identification. 相似文献
20.
Jansen Smith Marina C. Rillo Ádám T. Kocsis Maria Dornelas David Fastovich Huai-Hsuan M. Huang Lukas Jonkers Wolfgang Kiessling Qijian Li Lee Hsiang Liow Miranda Margulis-Ohnuma Stephen Meyers Lin Na Amelia M. Penny Kate Pippenger Johan Renaudie Erin E. Saupe Manuel J. Steinbauer Mauro Sugawara Adam Tomašovỳch John W. Williams Moriaki Yasuhara Seth Finnegan Pincelli M. Hull 《Global Ecology and Biogeography》2023,32(10):1680-1689